Volume 3 Issue 1 Article 4

Volume 3 Issue 1 Article 4 3-20-2020

CLINICAL AND IMMUNOLOGICAL CHARACTERISTIC OF ACUTE

CLINICAL AND IMMUNOLOGICAL CHARACTERISTIC OF ACUTE

DIARRHEAL DISEASES IN CHILDREN

DIARRHEAL DISEASES IN CHILDREN

Tashkent Pediatric Medical Institute, Uzbekistan., [email protected]

I.A. Kasimov

Tashkent Pediatric Medical Institute, Uzbekistan.

Follow this and additional works at: https://uzjournals.edu.uz/pediatrics Recommended Citation

Recommended Citation

Shadjalilova, M.S. and Kasimov, I.A. (2020) "CLINICAL AND IMMUNOLOGICAL CHARACTERISTIC OF ACUTE DIARRHEAL DISEASES IN CHILDREN," Central Asian Journal of Pediatrics: Vol. 3 : Iss. 1 , Article 4. Available at: https://uzjournals.edu.uz/pediatrics/vol3/iss1/4

DISEASES IN CHILDREN DISEASES IN CHILDREN

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CLINICAL AND IMMUNOLOGICAL CHARACTERISTIC OF ACUTE DIARRHEAL DISEASES IN CHILDREN

Shadjalilova M.S., Kasimov I.A.

Tashkent Pediatric Medical Institute

Abstract

Background. The issue of acute diarrheas among children has become even more urgent due to some climatic and social factors in Central Asia. It is characterized with wide-spread, an unfavorable course with the formation of a clinic syndrome of invasive diarrhea, severe complications and frequent transition to a chronic form. Our aim was comparative assessment of the clinical and immunological characteristics of acute diarrheal diseases in children.

Methods. We monitored young children with acute intestinal infections with established etiology (n=212), unknown etiology (n=48) and healthy children (n=32). A prospective study was conducted using general clinical, bacteriological and statistical methods.

Results. We studied the clinical characteristics of acute diarrhea of bacterial origin, depending on the age of the children, the etiological factor, the nature of feeding. The disease in most patients proceeds in moderate and severe forms, recovery lasts up to 3-4 weeks, the pathogens are resistant to antibiotics, the widespread infection caused by Clostridium difficile is caused.

Conclusion. The clinical picture of acute diarrhea in 97% of cases was manifested in a combined lesion of the gastrointestinal tract. The severity and adverse outcome were largely associated with extreme degrees of intoxication, severe electrolyte disturbances, the presence of primary and secondary immunodeficiency, and partially with background congenital pathology.

Key words: bacterial intestinal infections, diarrhea, children, dysbacteriosis, cytokines.

BACKGROUND

The problem of acute diarrheas in children in our region becomes even more urgent due to some climatic and social factors that contribute to their spread, an unfavorable course with the formation of a clinic syndrome of invasive diarrhea, severe complications and frequent transition to a chronic form. Today, in the structure of

infectious diseases, they are second only to respiratory viral infections. According to recent estimates, in the United States, children suffer an average of ten diarrheal episodes up to 5 years of age.

According to the WHO, more than 1 billion people suffer from acute respiratory infections annually, of which 65-70% are children under 5 years old and in 2017 the

number of deaths among children under five years of age associated with diarrheal diseases amounted to more than 1.8 million (Guidelines, 2013; Yushchuk et al, 2012; Kharchenko & Burkin, 2007; Shadzhalilova, 2015).

In the world, 58% of deaths in children under 5 years were due to infectious diseases, including 11% to diarrheal infections. In the general structure of infectious diseases, acute intestinal infections account for more than 40% of all hospitalized patients. In our country, studies are widely conducted on viral, viral and bacterial diarrheal diseases (Asilova, 2014; Tuychiev et al, 2013; Shadjalilova2015; Garcia Christia et al, 2012). Despite this, in the practical healthcare system, doctors often find it difficult to determine the management tactics of patients with acute bacterial infections of bacterial origin, especially when prescribing antibiotic therapy, because invasive diarrhea is becoming an increasingly important public health problem due to the development of multidrug resistance of pathogens (Eraliev, 2017; Meier et al, 2003). The effectiveness of the studies justifies the need to study the clinical features of acute diarrheal diseases in children, the optimization of therapeutic and preventive measures aimed at reducing the socio-economic costs of diarrhea diseases in children.

PURPOSE OF THE STUDY The aim of the study was to compare the clinical and immunological

characteristics of acute diarrheal diseases in children.

MATERIALS AND METHODS We observed young children with acute diarrheal diseases with clarified etiology (n-212), unspecified etiology (n-48) and healthy children (n-32). A prospective study was conducted using general clinical, bacteriological and statistical research methods.

We studied the clinical characteristics of bacterial diarrheal diseases depending on the age of the children, the etiological factor, and the nature of feeding.

RESULTS

Among the 260 children with observed diarrhea, there were 160 (62%) boys and 100 (38%) girls, including 43 (16.5%) organized and 217 (83.5%) unorganized girls. The distribution of patients by age shows that children aged 4 to 12 months were 104 (40.0%), from 1 year to 2 years old - 116 (44.6%), from 2 to 3 years - 40 (15.4%). It should be noted that a group of children 0-1 year old, in most cases were children aged 6 to 12 months. In our observations, the average age of children was 14.0 ± 8.34. Children of the second year of life accounted for 45% of the total number of examined patients with acute diarrhea. 85.7% of children were admitted to a hospital with acute onset of the disease. Assessing the severity of the condition of children, we noted that in most cases, acute diarrhea proceeded in moderate form in children (62% and 77.5%). However,

relapses of the disease were significantly more often observed in children under 1 year old (39.1%). A comparison of the frequency of detecting the severity of acute diarrhea depending on the age of the children showed a direct dependence of the severity on the age of the children. The etiology of pathogens of acute diarrheal diseases in 211 (81.7%) sick children was established by the bacteriological method of research. 139 (61.8%) patients underwent PCR diagnostics. Moreover, the causative agent of salmonellosis was detected in 62 (28%) patients, the causative agent of dysentery was detected in 63 (28%), Escherichia Coli was found in 51 (23%) and Clostridi deficille in 36 (16.0%).

Further, we analyzed the frequency of acute diarrhea depending on the etiological factor. In contrast to dysentery, salmonella infection was significantly more often recorded in children under the age of one year. In our studies, the predominant strain was Salmonella Typhimurium var Copengagen, a multiresist strain. The proportion of acute dysentery among acute diarrhea in children remains stably high and depends on their age. According to our observations, among hospitalized children, the incidence rate among children over one year of age is 3 times higher than among children under one year of age. Also, the role of Shigella Zonne has significantly increased and the number of isolated Shigella Flexneri strains has decreased,

which indicates good sanitary control of water supply population. The proportion of Escherichia infections in children aged 1 year was 14.4% and increased almost 2 times in patients aged 1-3 years (23%). Among children under the age of one year, 30.7% of cases are acute diarrhea of unknown etiology, which requires the improvement of laboratory diagnostic methods.

In the distribution of patients depending on the type of feeding, it was found that in most cases the children were mixed-fed - 115 (44.3%), breast-fed - 70 (26.9%), and artificial - 75 (28.8 %). With mixed and artificial feeding, sick children were more likely to arrive 1-3 days from the onset of the disease. On days 4–7, patients most often received with natural feeding. With artificial feeding more often (44%), there was a repeated admission of patients to the hospital. An analysis of the dependence of the form of the disease and the nature of feeding showed that most often diarrhea developed with mixed feeding. The highest percentage of severe course and relapse of the disease was observed in children who were breast-fed (65.2%) p> 0.01.

According to the topical lesion of the gastrointestinal tract, the compared groups did not differ significantly (Table 1), while acute diarrhea proceeded mainly in the form of gastroenterocolitis (42.4%) and gastroenteritis (35.3%).

Figure 1. Distribution of sick children according to the topical diagnosis of acute diarrhea

As can be seen from figure 1, the clinical picture of acute diarrhea in the observed sick children in 97% of cases was manifested in a combined lesion of the gastrointestinal tract and in 3% of cases showed symptoms of damage to the small intestine in the form of enteritis. It should be noted that the severity of bowel damage did not always correspond to the severity of the condition. The manifestation of hemocolitis was relatively more often observed in children aged 1 to 3 years. Isolated gastritis in the patients we observed was not observed.

Respiratory diseases: acute respiratory viral infection, obstructive bronchitis, pneumonia and sepsis (18.2% and 6%) were infectious and inflammatory concomitant diseases. Among the concomitant

pathologies, in addition to intestinal microbiocenosis disorders in children of the first year of life, PEP prevailed (57.6% and 37.6%); rickets - 48% and 25.6%.

An analysis of the comparative clinical characteristics of the symptom complex of acute diarrhea upon admission to the hospital for children under the age of 1 year (n = 104) and children from 1-3 years old (n = 156) showed the following results (table 1). The onset of the disease in children of both groups was usually acute, and amounted to 71.2% and 78.8%, respectively. The severity of the condition in children under 1 year and 1-3 years old was due, first of all, to violations of the water-electrolyte balance and the development of intestinal toxicosis. 0 5 10 15 20 25 30 35 40 45 Enteritis Gastroenteritis Gastroуnterocolitis Hemokolite Enterocolitis

Table 1. Comparative Clinical Characterization of Acute Symptoms upon Admission

Signs Children under 1 y/o. n=104 Children aged 1-3 y/o n=156 Abs % Abs %

Disease onset Acute 74 71,2 123 78,8

Gradual 30 28,8 33 21,1 Temperature Normal 15 14,4 21 13,4 >38 61 58,6 87 55,7 <38 28 27,0 48 30,8 Fatigue 104 100 156 100 Lethargy 104 100 156 100

Paleness, marbling of integument 102 98,0 156 100

Dry mucous membranes 104 100 156 100

Disorders of Sleep 58 55,8 79 50,6 Appetite 100 96,2 151 97,0 Language tightness 102 98,0 156 100 Nausea 58 55,8 95 60,8 Vomiting Single 58 55,8 85 60,8 Multiple 18 17,3 24 15,4 Abdominal pain 95 91,3 133 85,2 Bloating 68 65,4 93 59,6 Rumbling 59 56,7 88 56,4 Painful sigma 37 35,5 66 42,3

Tenesmus and its equivalents 23 22,1 57 36,5

Stool characteristics

Loose stool with mucus 74 71,2 103 66,0

Loose stool with mucus+blood 21 20,2 38 24,4

Watery, plentiful stools 8 7,6 15 9,6

Porridge-shaped 1 1,0 0 0 Stool frequency per day 3-5 35 33,7 38 28,6 5-10 58 55,8 79 50,6 12-15 11 10,5 27 17,3 >15 0 0 12 7,7 Hepatomegaly 36 34,6 56 35,8

The analysis showed that the clinical manifestations of acute intestinal infections in both groups of children showed manifold clinical manifestations. However, the symptoms of general intoxication were the most characteristic: fever - (58.6% and 55.7%, respectively), weakness, lethargy, pallor of the skin, sleep disturbances (55.8 and 50.6%, respectively), appetite (96.2 and 97.0%, respectively), tongue overlay in almost all sick children. The severity of both the general toxic syndrome and local manifestations varied and depended on age. So single vomiting was more often observed among children from 1-3 years old (60.8%) compared with children under 1 year old (55.8%). Repeated vomiting was observed in 18 (17.3%) children under 1 year old. In both groups there was a significant increase in syndromes - abdominal pain (91.3% and 85.2%, respectively); bloating - (65.4% and 59.6%, respectively); rumbling of the intestines (56.7% and 56.4%, respectively). Painful, spasmodic sigma and tenesmus, and its equivalents were observed relatively clearly in groups of children from 1-3 years old (35.5% and 42.5%, respectively). In addition to the main clinical manifestations of the disease - fever, pain, marked diarrhea was noted. More often, loose stools with mucus were observed (71.2% and 66.0%, respectively) and loose stools with mucus and blood were observed in 20.2% and 24.4%, respectively. So, the frequency of stool in children under 1 year old was 55.8%, in children aged 13 years old -50.6%, which certainly proves the prevailing

role of diarrhea syndrome especially in children.

Dyspeptic symptoms like abdominal pain occurred in 88.9%, with a duration of 6.5+0.72 days. Bloating - 61.1%, rumbling of the intestine - 66.7%, sigmoid colon pain 30.6%, tenesmus and its equivalents -25%, vomiting, with a single - in 50%. 27 (75%) sick children had loose stools with impurities of mucus, and 25% had streaks of blood. Moreover, more than half of patients with stool frequency were more than 8-10 times a day. The duration of diarrhea in days was -12.4+1.62. The generalization of the infectious process and the development of sepsis, especially with mixed infections, were also characteristic. An objective examination revealed hepatomegaly in 83.3% of patients, splenomegaly in 38.9%, pathological murmurs in the apex of the heart and wheezing in the lungs in 37%. In children of the first year of life, moderate dehydration was more characteristic in the clinical picture of diseases . The signs of dehydration were clinically manifested by exacerbation of facial features, retraction of the large fontanel and eyes, dry mucous membranes, decreased tissue turgor, and thirst. Toxico-dystrophic state was characteristic of sick children under the age of one year (p> 0.01). In children aged 1 year to 3 years, acute diarrhea was accompanied by dehydration and toxicosis I degree. Convulsive syndrome prevailed in the clinic - 15.8% of cases. We observed the development of all three types of dehydration, but in a larger number of patients, even with severe forms of the

disease, two hypertonic and isotonic prevailed.

Due to the fact that stool disorders persisted after resolving the inflammatory process and discontinuing antibiotic therapy, all children underwent a microbiological examination of feces. Bacteriologically, the diagnosis of intestinal disbacteriosis of various degrees was confirmed in 100% of cases, of which 33 (18.0%) – I degree, 102 (56.0%) –– II degree, and 34 (18.5%) –– III degree disbacteriosis.

An analysis of the colon microflora showed that in the studied children there were pronounced changes in the intestinal microbiocenosis, namely: 61.1% of children had no bifidobacteria, 66.7% had lactobacilli, while E. coli deficiency was noted in 38.8% of patients. Strains of E. coli with hemolytic activity were isolated in 22% of children. In some of the children, fungi of the genus Candida, Klebsiella and Proteus were sown in significant credits. Sanitation of the body was slow, and in one third of patients the pathogen continued to be sown at 3-4 weeks of illness. It should be noted that the clinical recovery of sick children was not always accompanied by a normalization of dysbiotic reactions. Upon

repeated examination, 36.4% of children retained intestinal disbacteriosis of varying degrees. Our studies show that if patients have clinical symptoms of intoxication and severe manifestations of diarrhea syndrome, the absence of pronounced dysbiotic disorders on the part of the intestinal microflora, which, in our opinion, is associated with the severity of the compensatory abilities of the children's body.

Studies on the cytokine status showed that patients with acute diarrhea have a significant increase in serum IL-1 level (Table 3). Thus, the content of the interleukin-1 cytokine in the peripheral blood serum in patients with salmonellosis was significantly increased to 73.0 ± 5.15 pg/ml, with dysentery to 74.7 ± 5.14 pg/ml, with escherichiosis to 25.2 ± 5, 26 pg/ml, with unidentified intestinal infection up to 88.7 ± 5.14 pg/ml at 5.46 ± 0.79 pg/ml in the control (p<0.001 in all cases). It should be noted that the smallest increase in interleukin-1 was observed with the pathogen E. Coli, and the maximum increase in the concentration of this cytokine was recorded in children with acute diarrhea of unknown etiology.

Table 3. Immunity indicators for some acute intestinal infections

Immunological indicators Control group (n=25) Salmonellosi s (n=22) Dysentery (n=20) Escherichia (n=16) Diarrhea of unknown etiology (n=18) IL-1β 5,46±0,79 73,0±5,15*** 74,7±5,14*** 25,2±5,26*** 88,7±5,14*** TNF-а 6,0±0,92 69,5±2,6*** 76,6±3,15*** 39,3±4,12*** 83,4±4,62*** IL-4 6,1±0,89 52,4±2,58*** 57,2±2,58*** 30,6±3,89*** 76,6±2,68*** IL-6 6,6±0,81 57,8±4,17*** 61,2±5,89*** 54,4±7,0*** 68,2±5,89***

Note: * P <0.05; ** P <0.01; *** P <0.001 DISCUSSIONS

To clarify the relationship and nature of the production of IL-4 in acute intestinal infections in children with various forms of infectious pathogen, we conducted a comparative analysis. So, in our studies, the content of the serum of IL-4 in the serum of peripheral blood was significantly increased to 52.4 ± 2.58 pg/ml in sick children with the Salmonella infectious pathogen, to 57.2 ± 2.58 pg/ml with the Shigella infectious pathogen. up to 30.6 ± 3.89 pg/ml with infectious pathogen E. Coli and up to 76.6 ± 2.68 pg/ml children with diarrhea of unknown etiology at 6.1 ± 0.89 pg/ml in control (p <0.001 in all cases).

An analysis of the parameters of the B-cell differentiation factor in the studied subgroups of sick children with diarrhea also revealed a high production of IL-6 by immunocompetent cells. As a result of statistical analysis, the highest level of IL-6 production (68.2 ± 5.89 pg/ml; p <0.001) was registered in the group of sick children with acute diarrhea of unknown etiology.

The production of IL-6 by

immunocompetent cells in case of salmonellosis (57.8 ± 4.17 pg/ml), dysentery (61.2 ± 5.89 pg/ml), and escherichiosis (54.4 ± 7.0 pg/ml) was almost equally high, significantly different from the group of practically healthy children. Thus, in the acute period of acute intestinal infection, an increase in serum levels of 1, TNF-a, IL-6, IL-4 was noted, the most pronounced, more than ten-fold increase of all studied

immunocytokines was observed from the side of IL-1, TNF -a, which indicates the possible initiation of differentiation of Th1 cells and increased cellular immunity.

The clinical picture of acute diarrheal diseases in children has now changed. The disease in most patients proceeds in moderate and severe forms, recovery is delayed up to 3-4 weeks, the pathogens are resistant to antibiotics. The clinical picture of the disease in 97% of cases was manifested in a combined lesion of the gastrointestinal tract.

CONCLUSIONS

The severity and adverse outcome were largely associated with extreme degrees of intoxication, severe electrolyte disturbances, the presence of primary and secondary immunodeficiency, and partially with background congenital pathology. The inflammatory response in children with acute intestinal infections, regardless of the nature of the pathogen, due to non-specific mediators - soluble cytokines IL-1, TNFα, IL-4, IL-6, was achieved by predominant production of the cytokines IL-1 and TNFα (with shigellosis IL- 6 and TNFα), immunocompetent cells with the subsequent development of the cellular mechanism of the body's defense against bacterial infection. Throughout the entire period of examination of patients, regardless of the etiology of the disease, anti-inflammatory IL-4 was detected, both in isolation and in combination with other cytokines.

STUDY LIMITATIONS

We could not perform sample size calculation for this research. There is a significant disproportion between the cohorts compared in the study. These factors can be a source of bias. Thus, further researches may be required with an adequate sample size and balanced arms to show more clear and exact results.

ACKNOWLEDGEMENTS We are grateful to the staff of the clinic of Tashkent Pediatric Medical Institute for the cooperation and support in our research. The parents of the participants kindly gave full written permission for this report.

ETHICAL APPROVAL

The ethical approval for the study was granted by the Committee of Ethical Approval for Researches under the Ministry of Health of the Republic of Uzbekistan.

CONSENT

Written informed consent was obtained from all participants’ parents of the research for publication of this paper and any accompanying information related to this study. A copy of the written consent is available for review by the authors.

CONFLICT OF INTEREST The authors declare that they have no competing interests.

FUNDING No funding sources to declare.

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